3'H-Cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione, 1,2-dihydro-17-hydroxy-, (1.alpha.,2.alpha.)-

Endpoint summary

Description of key information

Oral (Rat, GLP, equivalent to OECD TG 423): no evaluation possible [Schering AG, Report -draft-, 1994-03-25]

Oral (Rat, GLP, equivalent to OECD TG 423): LD50 > 2000 mg/kg [Schering AG, Report X026-draft-, 1995-07-19]

Dermal (Rat, GLP, equivalent to OECD TG 402): LD50 > 2000 mg/kg [Schering AG, Report No. X110 -draft-, 1996-08-06]

 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February -March 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

study was conducted prior to implementation of OECD TG 423

Deviations:

yes

Remarks:

two different sexes

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Doses:

2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

No deaths occurred as well as no deviations in weight development. Moreover, application of 2000 mg/kg was tolerated without any compound-related clinical or macroscopic pathological signs.

Interpretation of results:

GHS criteria not met

Conclusions:

the test item is of low acute oral toxicity

Executive summary:

The single oral administration of the test substance (ZK 12126) to male and female rats at a dose of 2000 mg/kg was tolerated without any mortality and compound-related clinical or macroscopic pathological signs. Therefore, the acute oral toxicity of 1,2 -Methylene-4,6-dien in rats is above 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Klimisch score 1

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November to December 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

yes

Remarks:

3 instead of 5 animals/sex used according to acute-toxic-class-method

Principles of method if other than guideline:

combined acute dermal toxicity and local irritation study

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

No mortality occurred. Moreover, no compound-related findings were observed in neither clinical observation nor body weight gain nor autopsy.

No local intolerance reactions at the application sites were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

the test item is of low acute dermal toxicity

Executive summary:

The single dermal administration of the test substance (ZK 12126) to male and female rats at a dose of 2000 mg/kg was tolerated without any mortality or compound-related clinical or macroscopic pathological signs. The acute dermal toxicity of 1,2 -Methylene-4,6 -dien in rats is therefore above 2000 mg/kg body weight.

No local intolerance reactions at the application sites were observed. The mean values of findings relevant for dermal classification (reddening, scab formation and swelling of the skin) at the time-points immediately after removal of the bandage and the substance, 24, 48 and 72 h after the end of administration were 0.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Klimisch score 1

Additional information

In a first study the re-analysis of the substance revealed a purity of only 48.2%, so that the results cannot be interpreted meaningfully.

In a second study with a batch of less impurity, the single oral administration of the test substance (ZK 12.126) to male and female rats at a dose of 2000 mg/kg was tolerated without any mortality and compound-related clinical or macroscopic pathological signs. Therefore, the acute oral toxicity of 1,2 -Methylene-4,6 -dien in rats is above 2000 mg/kg body weight.

 

The single dermal administration of the test substance (ZK 12126) to male and female rats at a dose of 2000 mg/kg was tolerated without any mortality or compound-related clinical or macroscopic pathological signs. The acute dermal toxicity of 1,2 -Methylene-4,6 -dien in rats is therefore above 2000 mg/kg body weight.

No local intolerance reactions at the application sites were observed. The mean values of findings relevant for dermal classification (reddening, scab formation and swelling of the skin) at the time-points immediately after removal of the bandage and the substance, 24, 48 and 72 h after the end of administration were 0.

Justification for classification or non-classification

Based on the study results a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.